Alpha-l-antitrypsin (AAT) is the major protease inhibitor in human serum. Although more than 90% of the population is found to contain protease inhibitor (Pi) type MM, a number of other variants have been found which are associated with a reduced serum concentration of the AAT. About 70-80,000 are homozygotes for the deficiency, gene Pi type ZZ, have serum levels of AAT which are a approximately 10-15% of normal and are strongly disposed to lung disease. In addition, in a number of other acute clinical conditions, including pancreatitis, respiratory failure, and cardiopulmonary bypass, there are indications that excessive proteolysis may be an important contribution factor. Previously, we have purified alpha-l-antitrypsin from Cohn fraction 1V-l, a blood fraction which has the potential to be utilized in large scale industrial processing. Our intention is to modify our reported procedure to obtain a preparation suitable for human testing. We plan, after appropriate experiments, to infuse this material into human volunteers, first with a small dose and only once, then gradually, if it is well received by recipients, to larger doses and with repeated infusion. These studies are designed to set the stage for clinical trial on the efficacy of AAT therapy for preventing chronic obstructive lung disease in ZZ individuals (and perhaps other individuals in early stages of disease), and in other acute illnesses.